… and the case for physics in biology

John Higgins pointed me to this superb discussion of the challenges for physicists posed by biological systems (Phillips, R., & Quake, S. (2006). The Biological Frontier of Physics Physics Today59 38-43). In this paper Rob Phillips and Stephen Quake offer — as a public service — three examples of big fascinating problems in biology that physicists could get their teeth into.

The first is the operation of molecular machines: “[t]hey are incredibly sophisticated, and they, not their manmade counterparts, represent the pinnacle of nanotechnology.” The authors choose ATP synthase as an example of a machine to marvel at. Run in the forwards direction — transforming the energy in a proton gradient into chemical energy — ATP synthase delivers approximately your body weight in ATP molecules per day. Run backwards, ATP synthase is a rotary motor, delivering 120 degrees of rotation for every ATP hydrolyzed; the absolute thermodynamic efficiency of this reaction has been estimated as up to 90%. That’s going to be hard to beat.

The second is the question of how such machines manage to operate reliably in an environment of significant noise. Noise, in this case, means fluctuations in energy levels due to thermal energy. This startling graph shows how the various energies that matter to a molecular machine scale with the size of an object — at the size of a molecular machine, all of these energies are roughly the same size.

What this means is that thermal energies are significant relative to what the authors call “deterministic forces”; thermal effects are large enough to allow conformational changes and the dissolution of hydrogen bonds, for example, as well as allowing charges to wander around fairly freely instead of sticking closely to their counter-charge. Because thermal energies are so relatively large — a molecular machine such as ATP synthase might deliver up to 100 pN-nm of work per ATP, while the thermal energy at room temperature would be about 4% of that — the question is how molecular machines manage to deliver consistent results in the face of constant battering. Phillips and Quake argue that a complete answer to this question will require integration of ideas from continuum mechanics, statistical mechanics, chemical kinetics, and fluid mechanics: the goal is to take the snapshots of protein structures that have been so arduously produced by structural biologists, and recreate the moving, jittering reality.

And the third example is understanding the collective behavior of biological systems, which are very far from equilibrium (equilibrium = death!) and dynamic (changing both in space and time). Biology, they argue, offers both motivation and specific problems to drive the development of a new physics of nonequilibrium systems. And while we’re at it, let’s have a physics that deals with solutions that are neither dilute nor homogeneous. The inside of the cell — the rapidly moving leading edge of a motile cell — these are situations in which the normal tools of physics do not apply.

Many types of people will gain from reading this article in full: physicists starting to think about what someone with their training can contribute to biology, biologists wondering how to frame their problem in a way to attract collaborators with training in physics, educators planning courses on the cutting edge of biology, or the cutting edge of physics. And finally modelers, who should meditate deeply on this comment: “Understanding collective effects in the cell will require merging two philosophical viewpoints. The first is that life is like a computer program: An infrastructure of machines carries out arbitrary instructions that are encoded into DNA software. The second viewpoint is purely physical: Life arises from a mixing together of chemicals that follow basic physical principles to self-assemble into an organism. Presumably, the repertoire of available behaviors is more limited in the latter. The two viewpoints are complementary, not incompatible: Either one could best describe cell behavior, depending on the particular situation.”

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§ One Response to … and the case for physics in biology

Anyone curious about this frontier of biology and physics can gain from the new textbook one of the authors has recently published – Physical Biology of the Cell. It is a didactic exploration of the physical aspects of life, ordered by physical subject and thus bringing together seemingly disparate subjects such as regulation by DNA bending, cytoskeletal filaments and viral capsids, giving a new perspective to many biological phenomena. For me it was the first time I really understood how biological regulation can be connected to entropy and enthalpy, and now they both make more sense.